PTP1C INCREASES IN THE DEAFFERENTED AUDITORY BRAINSTEM

星形胶质细胞对中枢神经系统(CNS)损伤的反应方式 对神经元的存活和再生既有支持也有抑制作用。 以前对星形胶质细胞对损伤和疾病的反应的研究已经 主要集中在形态变化上；包括增殖， 过程延长，神经胶质中间体水平增加 丝状蛋白，GFAP。这些胶质反应被认为是 不利于再生，然而，一些星形胶质细胞已被证明 参与似乎能促进再生的过程。这些措施包括 神经元碎片的吞噬作用和细胞外两者的合成 基质蛋白和多种神经营养因子。一种有用的方法来 鉴定参与生长促进过程的星形胶质细胞是为了研究 参与星形胶质细胞功能的分子过程 预期不同的分子级联可能在生长过程中启动- 促进星形胶质细胞与抑制生长星形胶质细胞。 越来越多的证据表明，蛋白质之间的平衡 磷酸化和去磷酸化调节许多细胞功能， 蛋白质酪氨酸磷酸化与这两种情况都有关联 星形胶质细胞的增殖和分化。磷酸化状态 蛋白质在酪氨酸残基上的比例受 蛋白酪氨酸激酶(PTKs)可磷酸化酪氨酸残基和 蛋白质酪氨酸磷酸酶(PTPs)可使酪氨酸去磷酸化 残留物。我们在雏鸡的听觉中发现了星形胶质细胞的一个亚群 酪氨酸磷酸酶PTP1C免疫阳性的脑干。 在去除耳蜗后，听觉中有一个显著的增加。 脑干核群中PTP1C的数目与大细胞数目有关 阳性星形胶质细胞及其免疫阳性纤维的长度。 这种增加似乎并不局限于含有GFAP的 星形胶质细胞与胶质细胞增殖无关。建议数 实验旨在确定这些PTP1C阳性 星形胶质细胞参与支持神经元的过程 去神经传入后的存活和阐明细胞外 增强这些星形胶质细胞中PTP1C免疫反应性的信号。它是 希望对分子过程有更完整的了解 参与星形胶质细胞的激活将提供对生长的洞察- 星形胶质细胞的促生长和抑制生长功能。这又反过来， 可能允许开发临床相关的策略来改善 损伤后神经元的存活和再生。

Astrocytes respond to central nervous system (CNS) injury in ways that are both supportive and inhibitory of neuronal survival-and regeneration. Previous studies of the astrocytic response to injury and disease have focused primarily on morphological changes; including proliferation, process extension, and increased levels of the glial intermediate filament protein, GFAP. These gliotic responses are thought to be detrimental to regeneration, however some astrocytes have been shown to engage in processes which appear to promote regeneration. These include phagocytosis of neuronal debris, and synthesis of both extracellular matrix proteins and numerous neurotrophic factors. A useful approach to identifying astrocytes engaged in growth promoting processes is to study the molecular processes involved in astrocyte function with the expectation that different molecular cascades may be initiated in growth- promoting vs. growth-inhibiting astrocytes. Accumulating evidence suggests that the balance between protein phosphorylation and dephosphorylation modulates many cellular functions, and protein tyrosine phosphorylation has been implicated in both astrocyte proliferation and differentiation. The phosphorylation state of proteins on tyrosine residues is regulated by the balance between protein tyrosine kinases (PTKs) which phosphorylate tyrosine residues and protein tyrosine phosphatases (PTPs) which dephosphorylate tyrosine residues. We have found a subset of astrocytes in the chick auditory brainstem that are immunopositive for the tyrosine phosphatase PTP1C. Following cochlea removal, there is a marked increase within the auditory brainstem nucleus, n. Magnocellularis (NM) both in the number of PTP1C positive astrocytes and in the length of their immunopositive fibers. This increase does not appear to be localized to GFAP-containing astrocytes and is not correlated with glial proliferation. The proposed experiments are designed to determine whether these PTP1C-positive astrocytes are involved in processes which are supportive of neuron survival following deafferentation and to elucidate the extracellular signals that increase PTP1C-immunoreactivity in these astrocytes. It is hoped that a more complete understanding of the molecular processes involved in astrocyte activation will provide insight into the growth- promoting and growth-inhibiting functions of astrocytes. This, in turn, may allow the development of clinically relevant strategies for improving neuronal survival and regeneration following injury.